                         SEQUENCE LISTING

<110>  Metaclipse Therapeutics Corporation
       Emory University
 
<120>  METHODS OF TREATING CANCER USING A COMBINATION OF TUMOR MEMBRANE VESICLES AND METFORMIN

<130>  10798-004WO1

<160>  10    

<170>  PatentIn version 3.5

<210>  1
<211>  288
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  1

Met Gly His Thr Arg Arg Gln Gly Thr Ser Pro Ser Lys Cys Pro Tyr 
1               5                   10                  15      


Leu Asn Phe Phe Gln Leu Leu Val Leu Ala Gly Leu Ser His Phe Cys 
            20                  25                  30          


Ser Gly Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu 
        35                  40                  45              


Ser Cys Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile 
    50                  55                  60                  


Tyr Trp Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp 
65                  70                  75                  80  


Met Asn Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr 
                85                  90                  95      


Asn Asn Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly 
            100                 105                 110         


Thr Tyr Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg 
        115                 120                 125             


Glu His Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr 
    130                 135                 140                 


Pro Ser Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile 
145                 150                 155                 160 


Ile Cys Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu 
                165                 170                 175     


Glu Asn Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp 
            180                 185                 190         


Pro Glu Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met 
        195                 200                 205             


Thr Thr Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg 
    210                 215                 220                 


Val Asn Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro 
225                 230                 235                 240 


Asp Asn Leu Leu Pro Ser Trp Ala Ile Thr Leu Ile Ser Val Asn Gly 
                245                 250                 255     


Ile Phe Val Ile Cys Cys Leu Thr Tyr Cys Phe Ala Pro Arg Cys Arg 
            260                 265                 270         


Glu Arg Arg Arg Asn Glu Arg Leu Arg Arg Glu Ser Val Arg Pro Val 
        275                 280                 285             


<210>  2
<211>  208
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  2

Val Ile His Val Thr Lys Glu Val Lys Glu Val Ala Thr Leu Ser Cys 
1               5                   10                  15      


Gly His Asn Val Ser Val Glu Glu Leu Ala Gln Thr Arg Ile Tyr Trp 
            20                  25                  30          


Gln Lys Glu Lys Lys Met Val Leu Thr Met Met Ser Gly Asp Met Asn 
        35                  40                  45              


Ile Trp Pro Glu Tyr Lys Asn Arg Thr Ile Phe Asp Ile Thr Asn Asn 
    50                  55                  60                  


Leu Ser Ile Val Ile Leu Ala Leu Arg Pro Ser Asp Glu Gly Thr Tyr 
65                  70                  75                  80  


Glu Cys Val Val Leu Lys Tyr Glu Lys Asp Ala Phe Lys Arg Glu His 
                85                  90                  95      


Leu Ala Glu Val Thr Leu Ser Val Lys Ala Asp Phe Pro Thr Pro Ser 
            100                 105                 110         


Ile Ser Asp Phe Glu Ile Pro Thr Ser Asn Ile Arg Arg Ile Ile Cys 
        115                 120                 125             


Ser Thr Ser Gly Gly Phe Pro Glu Pro His Leu Ser Trp Leu Glu Asn 
    130                 135                 140                 


Gly Glu Glu Leu Asn Ala Ile Asn Thr Thr Val Ser Gln Asp Pro Glu 
145                 150                 155                 160 


Thr Glu Leu Tyr Ala Val Ser Ser Lys Leu Asp Phe Asn Met Thr Thr 
                165                 170                 175     


Asn His Ser Phe Met Cys Leu Ile Lys Tyr Gly His Leu Arg Val Asn 
            180                 185                 190         


Gln Thr Phe Asn Trp Asn Thr Thr Lys Gln Glu His Phe Pro Asp Asn 
        195                 200                 205             


<210>  3
<211>  126
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  3

Lys Ala Met His Val Ala Gln Pro Ala Val Val Leu Ala Ser Ser Arg 
1               5                   10                  15      


Gly Ile Ala Ser Phe Val Cys Glu Tyr Ala Ser Pro Gly Lys Ala Thr 
            20                  25                  30          


Glu Val Arg Val Thr Val Leu Arg Gln Ala Asp Ser Gln Val Thr Glu 
        35                  40                  45              


Val Cys Ala Ala Thr Tyr Met Met Gly Asn Glu Leu Thr Phe Leu Asp 
    50                  55                  60                  


Asp Ser Ile Cys Thr Gly Thr Ser Ser Gly Asn Gln Val Asn Leu Thr 
65                  70                  75                  80  


Ile Gln Gly Leu Arg Ala Met Asp Thr Gly Leu Tyr Ile Cys Lys Val 
                85                  90                  95      


Glu Leu Met Tyr Pro Pro Pro Tyr Tyr Leu Gly Ile Gly Asn Gly Ala 
            100                 105                 110         


Gln Ile Tyr Val Ile Asp Pro Glu Pro Cys Pro Asp Ser Asp 
        115                 120                 125     


<210>  4
<211>  329
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Asp Pro Gln Cys Thr Met Gly Leu Ser Asn Ile Leu Phe Val Met 
1               5                   10                  15      


Ala Phe Leu Leu Ser Gly Ala Ala Pro Leu Lys Ile Gln Ala Tyr Phe 
            20                  25                  30          


Asn Glu Thr Ala Asp Leu Pro Cys Gln Phe Ala Asn Ser Gln Asn Gln 
        35                  40                  45              


Ser Leu Ser Glu Leu Val Val Phe Trp Gln Asp Gln Glu Asn Leu Val 
    50                  55                  60                  


Leu Asn Glu Val Tyr Leu Gly Lys Glu Lys Phe Asp Ser Val His Ser 
65                  70                  75                  80  


Lys Tyr Met Gly Arg Thr Ser Phe Asp Ser Asp Ser Trp Thr Leu Arg 
                85                  90                  95      


Leu His Asn Leu Gln Ile Lys Asp Lys Gly Leu Tyr Gln Cys Ile Ile 
            100                 105                 110         


His His Lys Lys Pro Thr Gly Met Ile Arg Ile His Gln Met Asn Ser 
        115                 120                 125             


Glu Leu Ser Val Leu Ala Asn Phe Ser Gln Pro Glu Ile Val Pro Ile 
    130                 135                 140                 


Ser Asn Ile Thr Glu Asn Val Tyr Ile Asn Leu Thr Cys Ser Ser Ile 
145                 150                 155                 160 


His Gly Tyr Pro Glu Pro Lys Lys Met Ser Val Leu Leu Arg Thr Lys 
                165                 170                 175     


Asn Ser Thr Ile Glu Tyr Asp Gly Val Met Gln Lys Ser Gln Asp Asn 
            180                 185                 190         


Val Thr Glu Leu Tyr Asp Val Ser Ile Ser Leu Ser Val Ser Phe Pro 
        195                 200                 205             


Asp Val Thr Ser Asn Met Thr Ile Phe Cys Ile Leu Glu Thr Asp Lys 
    210                 215                 220                 


Thr Arg Leu Leu Ser Ser Pro Phe Ser Ile Glu Leu Glu Asp Pro Gln 
225                 230                 235                 240 


Pro Pro Pro Asp His Ile Pro Trp Ile Thr Ala Val Leu Pro Thr Val 
                245                 250                 255     


Ile Ile Cys Val Met Val Phe Cys Leu Ile Leu Trp Lys Trp Lys Lys 
            260                 265                 270         


Lys Lys Arg Pro Arg Asn Ser Tyr Lys Cys Gly Thr Asn Thr Met Glu 
        275                 280                 285             


Arg Glu Glu Ser Glu Gln Thr Lys Lys Arg Glu Lys Ile His Ile Pro 
    290                 295                 300                 


Glu Arg Ser Asp Glu Ala Gln Arg Val Phe Lys Ser Ser Lys Thr Ser 
305                 310                 315                 320 


Ser Cys Asp Lys Ser Asp Thr Cys Phe 
                325                 


<210>  5
<211>  219
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Cys Pro Ala Arg Ser Leu Leu Leu Val Ala Thr Leu Val Leu Leu 
1               5                   10                  15      


Asp His Leu Ser Leu Ala Arg Asn Leu Pro Val Ala Thr Pro Asp Pro 
            20                  25                  30          


Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val 
        35                  40                  45              


Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys 
    50                  55                  60                  


Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser 
65                  70                  75                  80  


Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys 
                85                  90                  95      


Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala 
            100                 105                 110         


Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr 
        115                 120                 125             


Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys 
    130                 135                 140                 


Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu 
145                 150                 155                 160 


Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr 
                165                 170                 175     


Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys 
            180                 185                 190         


Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr 
        195                 200                 205             


Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
    210                 215                 


<210>  6
<211>  328
<212>  PRT
<213>  Homo sapiens

<400>  6

Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu 
1               5                   10                  15      


Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val 
            20                  25                  30          


Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu 
        35                  40                  45              


Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln 
    50                  55                  60                  


Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys 
65                  70                  75                  80  


Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val 
                85                  90                  95      


Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp 
            100                 105                 110         


Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe 
        115                 120                 125             


Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp 
    130                 135                 140                 


Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser 
                165                 170                 175     


Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu 
            180                 185                 190         


Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile 
        195                 200                 205             


Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr 
    210                 215                 220                 


Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn 
225                 230                 235                 240 


Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp 
                245                 250                 255     


Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr 
            260                 265                 270         


Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg 
        275                 280                 285             


Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala 
    290                 295                 300                 


Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser 
305                 310                 315                 320 


Glu Trp Ala Ser Val Pro Cys Ser 
                325             


<210>  7
<211>  607
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  7

Thr Gln Val Cys Thr Gly Thr Asp Met Lys Leu Arg Leu Pro Ala Ser 
1               5                   10                  15      


Pro Glu Thr His Leu Asp Met Leu Arg His Leu Tyr Gln Gly Cys Gln 
            20                  25                  30          


Val Val Gln Gly Asn Leu Glu Leu Thr Tyr Leu Pro Thr Asn Ala Ser 
        35                  40                  45              


Leu Ser Phe Leu Gln Asp Ile Gln Glu Val Gln Gly Tyr Val Leu Ile 
    50                  55                  60                  


Ala His Asn Gln Val Arg Gln Val Pro Leu Gln Arg Leu Arg Ile Val 
65                  70                  75                  80  


Arg Gly Thr Gln Leu Phe Glu Asp Asn Tyr Ala Leu Ala Val Leu Asp 
                85                  90                  95      


Asn Gly Asp Pro Leu Asn Asn Thr Thr Pro Val Thr Gly Ala Ser Pro 
            100                 105                 110         


Gly Gly Leu Arg Glu Leu Gln Leu Arg Ser Leu Thr Glu Ile Leu Lys 
        115                 120                 125             


Gly Gly Val Leu Ile Gln Arg Asn Pro Gln Leu Cys Tyr Gln Asp Thr 
    130                 135                 140                 


Ile Leu Trp Lys Asp Ile Phe His Lys Asn Asn Gln Leu Ala Leu Thr 
145                 150                 155                 160 


Leu Ile Asp Thr Asn Arg Ser Arg Ala Cys His Pro Cys Ser Pro Met 
                165                 170                 175     


Cys Lys Gly Ser Arg Cys Trp Gly Glu Ser Ser Glu Asp Cys Gln Ser 
            180                 185                 190         


Leu Thr Arg Thr Val Cys Ala Gly Gly Cys Ala Arg Cys Lys Gly Pro 
        195                 200                 205             


Leu Pro Thr Asp Cys Cys His Glu Gln Cys Ala Ala Gly Cys Thr Gly 
    210                 215                 220                 


Pro Lys His Ser Asp Cys Leu Ala Cys Leu His Phe Asn His Ser Gly 
225                 230                 235                 240 


Ile Cys Glu Leu His Cys Pro Ala Leu Val Thr Tyr Asn Thr Asp Thr 
                245                 250                 255     


Phe Glu Ser Met Pro Asn Pro Glu Gly Arg Tyr Thr Phe Gly Ala Ser 
            260                 265                 270         


Cys Val Thr Ala Cys Pro Tyr Asn Tyr Leu Ser Thr Asp Val Gly Ser 
        275                 280                 285             


Cys Thr Leu Val Cys Pro Leu His Asn Gln Glu Val Thr Ala Glu Asp 
    290                 295                 300                 


Gly Thr Gln Arg Cys Glu Lys Cys Ser Lys Pro Cys Ala Arg Val Cys 
305                 310                 315                 320 


Tyr Gly Leu Gly Met Glu His Leu Arg Glu Val Arg Ala Val Thr Ser 
                325                 330                 335     


Ala Asn Ile Gln Glu Phe Ala Gly Cys Lys Lys Ile Phe Gly Ser Leu 
            340                 345                 350         


Ala Phe Leu Pro Glu Ser Phe Asp Gly Asp Pro Ala Ser Asn Thr Ala 
        355                 360                 365             


Pro Leu Gln Pro Glu Gln Leu Gln Val Phe Glu Thr Leu Glu Glu Ile 
    370                 375                 380                 


Thr Gly Tyr Leu Tyr Ile Ser Ala Trp Pro Asp Ser Leu Pro Asp Leu 
385                 390                 395                 400 


Ser Val Phe Gln Asn Leu Gln Val Ile Arg Gly Arg Ile Leu His Asn 
                405                 410                 415     


Gly Ala Tyr Ser Leu Thr Leu Gln Gly Leu Gly Ile Ser Trp Leu Gly 
            420                 425                 430         


Leu Arg Ser Leu Arg Glu Leu Gly Ser Gly Leu Ala Leu Ile His His 
        435                 440                 445             


Asn Thr His Leu Cys Phe Val His Thr Val Pro Trp Asp Gln Leu Phe 
    450                 455                 460                 


Arg Asn Pro His Gln Ala Leu Leu His Thr Ala Asn Arg Pro Glu Asp 
465                 470                 475                 480 


Glu Cys Val Gly Glu Gly Leu Ala Cys His Gln Leu Cys Ala Arg Gly 
                485                 490                 495     


His Cys Trp Gly Pro Gly Pro Thr Gln Cys Val Asn Cys Ser Gln Phe 
            500                 505                 510         


Leu Arg Gly Gln Glu Cys Val Glu Glu Cys Arg Val Leu Gln Gly Leu 
        515                 520                 525             


Pro Arg Glu Tyr Val Asn Ala Arg His Cys Leu Pro Cys His Pro Glu 
    530                 535                 540                 


Cys Gln Pro Gln Asn Gly Ser Val Thr Cys Phe Gly Pro Glu Ala Asp 
545                 550                 555                 560 


Gln Cys Val Ala Cys Ala His Tyr Lys Asp Pro Pro Phe Cys Val Ala 
                565                 570                 575     


Arg Cys Pro Ser Gly Val Lys Pro Asp Leu Ser Tyr Met Pro Ile Trp 
            580                 585                 590         


Lys Phe Pro Asp Glu Glu Gly Ala Cys Gln Pro Cys Pro Ile Asn 
        595                 600                 605         


<210>  8
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  8

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala 
            20                  25                  30          


Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  9
<211>  55
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  9

Gly Thr Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys 
1               5                   10                  15      


Val Asn Gly Gly Glu Cys Phe Met Val Lys Asp Leu Ser Asn Pro Ser 
            20                  25                  30          


Arg Tyr Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln 
        35                  40                  45              


Asn Tyr Val Met Ala Ser Phe 
    50                  55  


<210>  10
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  10

Thr Tyr Leu Pro Ala Asn Ala Ser Leu 
1               5                   


<210>  11
<211>  76
<212>  PRT
<213>  Homo sapiens

<400>  11

Ile Thr Lys Ala Gly Leu Gln Val Tyr Asn Lys Cys Trp Lys Phe Glu 
1               5                   10                  15      


His Cys Asn Phe Asn Asp Val Thr Thr Arg Leu Arg Glu Asn Glu Leu 
            20                  25                  30          


Thr Tyr Tyr Cys Cys Lys Lys Asp Leu Cys Asn Phe Asn Glu Gln Leu 
        35                  40                  45              


Glu Asn Gly Gly Thr Ser Leu Ser Glu Lys Thr Val Leu Leu Leu Val 
    50                  55                  60                  


Thr Pro Phe Leu Ala Ala Ala Trp Ser Leu His Pro 
65                  70                  75      





